Metabonomics Study And Applications On Diseases And Drug Intervention

In present dissertation, with the guidance of chemomics-integrated global systems biology, we carried out metabonomics researches of different diseases and chemomics study of Traditional Chinese Medicine based on the UPLC/MS strategy. The applicability of metabonomics approach in diseases diagnosis and drug intervention was mainly investigated.1. A UPLC/Q-TOF-MS method for urinary metabolic fingerprinting of Premenstrual syndrome model rats with liver-qi invasion was established. The effect of Chinese medicine Jingqianping granule was investigated using metabonomic study. The time-dependent metabolic variations was visualized in model group and treatment group and revealed effective remedy of Jingqianping granule for PMS. Both PCA and PLS-DA were used to screen potential biomarkers. Meanwhile, an artificial neural network (ANNs) was applied for metabonomics data mining. The results showed ANNs was available in modeling complex metabonomic data and discovering hidden knowledge about potential bio-markers associated with the development of disease.2. Based on the technique of UPLC/TOF-MS, a metabonomics method for the research of plasma of gene knockout mice and patients with coronary heart disease was established and applied to track the effect of D-4F intervention. Phospholipid lysophosphatidylcholine (LPC) was identified as one of potential diagnosis markers and D-4F reduced the content of LPC. Metabolic profiling of patients with coronary heart disease (HP and no-HP) and healthy controls were analyzed with PCA, PLS-DA, OPLS-DA and multiple test. The cluster results showed significant alterations in metabolite expression patterns and the metabolites with significant inter-group differences were identified as potential biomarkers. These results suggest that the metabonomics strategy can be potentially appied to coronary heart disease diagnosis or classification.3. UPLC/TOF-MS based metabonomic approach was used to investigate the effect of combined caffein and promethazine on prevention and treatment of motion sickness. The differencs between urine of promethazine alone medication and combined caffein were analyzed with OPLS-DA. Several potential biomarkers that are involved in biosynthesis of neurotransmitter were identified. Meanwhile, drug metabolites were screened in metabolite profiling according to the accurate mass and fragmentation information.4. A new method using UPLC/Q-TOF-MS was developed for the rapid qualitative and quantitative analysis of Asian ginseng (Panax ginseng C.A.Meyer) in adulterated American ginseng (Panax quinquefolium L.) preparations within 2 minutes. The advantages of hybrid Q-TOF mass spectrometry not only include quality detection capability, sensitivity, but also include accurate measurement, reliable chemical fragmentation, which make the structure elucidations easier.